Meryl and Otacon
Series: Metal Gear
Meryl Silverburgh and Hal Emmerich (a.k.a. Otacon) each occupy key and distinct roles as sidekicks in Solid Snake's world.
Meryl fills the role of a romantic interest and female Snake equivalent and Otacon delivers doses of sharp-minded exposition and comic relief. Seeing as the Metal Gear series is always willing to tinker with its cast's roles and juggle lineups to tell different stories, each character could feasibly handle a solo title.
Alternately, the pair could team up, sort like how Sonya Blade and Jax did in Mortal Kombat: Special Forces (except this game won't suck). The second situation could present the problem of one character potentially falling behind the other in importance, but we'll leave the logistics up to Konami.